Abstract
Autoantibodies directed against specific human aminoacyl-tRNA synthetases have been associated with a clinical picture including myositis, arthritis, interstitial lung disease and other features that has been referred to as the "anti-synthetase syndrome". Anti-asparaginyl-tRNA synthetase autoantibodies (anti-KS), the most recently described anti-synthetase autoantibodies, are directed against human cytosolic asparaginyl-tRNA synthetase and neutralize specifically its activity. Here we show that these antibodies recognize two epitopes on the human enzyme, an N-terminal epitope reactive in immunoblot experiments and a heat-labile epitope in the catalytic domain. In contrast to the well studied anti-Jo-1 autoantibodies anti-KS when bound to the synthetase increase the affinity of the synthetase for its tRNA substrate and prevent aminoacylation without interfering with the amino acid activation step.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acylation / drug effects
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Amino Acyl-tRNA Synthetases / antagonists & inhibitors
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Amino Acyl-tRNA Synthetases / genetics
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Amino Acyl-tRNA Synthetases / immunology*
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Amino Acyl-tRNA Synthetases / metabolism*
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Antibody Specificity / immunology
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Aspartate-tRNA Ligase*
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Autoantibodies / immunology*
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Autoantibodies / pharmacology
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Binding, Competitive
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Catalytic Domain
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Epitope Mapping
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Epitopes / immunology
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Humans
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Immune Sera / immunology
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Immune Sera / pharmacology
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Molecular Sequence Data
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Mutation
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Neutralization Tests
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RNA, Transfer, Amino Acyl*
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RNA, Transfer, Asp / genetics
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RNA, Transfer, Asp / metabolism*
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
Substances
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Autoantibodies
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Epitopes
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Immune Sera
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RNA, Transfer, Amino Acyl
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RNA, Transfer, Asp
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Recombinant Proteins
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Amino Acyl-tRNA Synthetases
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Aspartate-tRNA Ligase
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asparaginyl-tRNA synthetase